1. Field of the Invention
The present invention relates to the field of endovascular embolic materials for embolization in abnormal microvascular beds or nidi, and in particular to a semisolid-semiliquid endovascular embolic multipurpose ointment and a corresponding soft particle form of embolic beads.
2. Description of Related Art
Endovascular embolic materials, which are currently used for embolization of abnormal microvascular beds or nidi, include injectable solid particles, sutures, fibers, tissue or sponge fragments, as well as liquid agents such as glues and emulsions. In the case of brain arteriovenous malformation embolization, almost all of the solid embolic materials are nonradio-opaque. Most of these materials are rapidly biodegradable; for example, Avitene fibers, sponge and dura fragments, protein microbeads and the like, which offer only temporary embolization. See Lon F. Alexander et al., "The History of Endovascular Therapy," Neurosurgery Clinics of North America, 5 (3) at 383-391 (1994). The nondegradable materials, such as polyvinyl alcohol (PVA) particles, silk sutures and the like, have a high rate of recanalization and collateralization that is, a tendency for blocked vessels to reopen and a tendency for parallel vessel paths to develop, respectively. This not withstanding that these materials may permanently remain at the embolized sites.
It is believed that the spontaneous thrombolysis (i.e., dissolving of the blockage) and angiogenesis (i.e., growth of new vessels) are the main contributing mechanisms to this recanalization and collateralization. Furthermore, these prior art types of solid materials usually tend to stay proximate to the injection site instead of moving into the nidus itself due to the lack of deformability of these materials. As a result, a considerable number of nidus vessels remain anatomically open even though the whole arteriovenous malformation nidus is angiographically occluded. These remaining portions, which lack embolic material, offer beds for recurrence. See for example Mazen H. Khayata et al., "Materials and Embolic Agents for Endovascular Treatment," Neurosurgery Clinics of North America, 5 (3) at 475-84 (1994).
Many liquid embolic materials have unfavorable properties. For example, while liquid glue, such as isobutyl-2-cyanoarylate (IBCA) has a good mobility rate inside the delivery microcatheter, it is unpredictable inside the nidus due to difficulties in controlling its polymerization rate. An optimal result may be achieved if a glue with suitable adjusted hardening time is delivered into the desired dominant portion of the arteriovenous malformation nidus. However, further treatment, such as surgical removal or radiation, is usually required in most cases using these liquid materials. See Fournier et al., "Endovascular Treatment of Intracerebral Arteriovenous Malformations: Experience in 49 Cases," Journal of Neurosurgery, 75 (2) at 228-33 (1991).
In the case of malignant tumor endovascular treatments, such as hepatocellular carcinoma embolizations, the liquid emulsions made of Lipiodol and aqueous anticarcinogenic solutions show much better effects than most solid drug carrier particles. This is because the liquid emulsions have better mobility and can embolize malignant microvascular beds more extensively than solid particles. In addition, the emulsion can carry more anticarcinogens into the tumor. See Ichida et al., "Therapeutic Effect of a CDDP-Epirubicin-Lipiodol Emulsion on Advanced Hepatocellular Carcinoma," Cancer Chemotherapy and Pharmacology, 33 suppl., S74-8 (1994).
However, nonsolidifiable liquid material, such as Lipiodol emulsion, cannot be applied in the treatment of arteriovenous malformation because the emulsion would be washed away within minutes. Liquid emulsions exhibit less friction in the embolized microvascular beds, so that in some high blood flow tumors, especially those with intratumoral microshuntings similar to the arteriovenous malformation nidi, the delivered embolic agent can be washed away within hours or days. See Kan et al., "Distribution and Effect of Iodized Poppyseed Oil in the Liver After Hepatic Artery Embolication: Experimental Study in Several Animal Species," Radiology, 186:861-6 (1993); and Luo et al., "Treatment of Hepatocellular Carcinoma by Transarterial Approach," Chung-Huai Hsueh Tsa Chih Chinese Medical Journal, 73:158-60 (1993).
What is needed is a more stable embolic carrier with a better relative friction and mobility to produce a longer lasting embolization for preventing or retarding thrombolysis or revascularization and for maintaining a higher drug concentration within the target tumors when used for drug delivery. Embolic agents that resulted in scar formation which blocks new vascular growth would be especially favored. Therefore in general what is needed is an improved therapeutic result in endovascular embolizations which is not subject to the disadvantages discussed above in connection with each of the prior art embolic materials.